Staphylococcus aureus is the leading bacterial pathogen of the musculoskeletal system, and its potential to cause disease in bone appears to involve interactions between specific bacterial surface adhesins and extracellular matrix proteins such as collagen, bone sialoprotein, and fibronectin. The ability to bind each of these host proteins is often mediated by a distinct adhesin and, in at least one case, by an adhesin of broad specificity (the Map protein), which binds collagen, bone sialoprotein, fibronectin, and osteopontin. Genes encoding adhesins for collagen, fibronectin, and osteopontin have been identified, although a gene product specifically recognizing bone sialoprotein has not yet been characterized. Strains isolated from patients suffering from osteomyelitis generally exhibit a high binding capacity for one or more of these host matrix proteins. In Specific Aim One, the principal investigator proposes to examine clinical isolates obtained from patients with osteomyelitis for their ability to bind host matrix proteins in a biochemical assay and for the presence of adhesin genes on Southern blot. In Specific Aim 2 he will use site-directed mutagenesis to render clinical isolates unable to bind one or more of the ECM proteins. In Specific Aim 3, he will study the effect of each mutation on the ability to cause osteomyelitis in a rabbit model of acute, exogenous disease.